A Study to Evaluate the Dose Response Based on the Efficacy, Safety and Tolerability of Bimekizumab in Subjects With Active Psoriatic Arthritis Which is a Type of Inflammatory Arthritis (BE ACTIVE)

A Multicenter, Phase 2B, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study to Evaluate the Efficacy and Safety of Bimekizumab in Active Psoriatic Arthritis

This is a study to evaluate the dose response based on the efficacy, safety and tolerability of bimekizumab in subjects with active psoriatic arthritis.

Study Overview

• Status: Completed
• Conditions: Psoriatic Arthritis
• Intervention / Treatment: Other: Placebo; Drug: Bimekizumab

• Study Type: Interventional
• Enrollment (Actual): 206
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia
    • Pa0008 205
  • Olomouc, Czechia
    • Pa0008 207
  • Praha 11, Czechia
    • Pa0008 210
  • Praha 2, Czechia
    • Pa0008 202
  • Praha 4, Czechia
    • Pa0008 201
  • Praha 4, Czechia
    • Pa0008 209
  • Zlin, Czechia
    • Pa0008 203
• Germany
  • Cologne, Germany
    • Pa0008 302
  • Erlangen, Germany
    • Pa0008 309
  • Hamburg, Germany
    • Pa0008 304
  • Ratingen, Germany
    • Pa0008 301
• Hungary
  • Budakeszierdo, Hungary
    • Pa0008 403
  • Veszprem, Hungary
    • Pa0008 401
• Poland
  • Bialystok, Poland
    • Pa0008 452
  • Elblag, Poland
    • Pa0008 453
  • Elblag, Poland
    • Pa0008 456
  • Krakow, Poland
    • Pa0008 455
  • Poznan, Poland
    • Pa0008 451
  • Torun, Poland
    • Pa0008 450
  • Warszawa, Poland
    • Pa0008 454
  • Warszawa, Poland
    • Pa0008 459
  • Wroclaw, Poland
    • Pa0008 465
• Russian Federation
  • Moscow, Russian Federation
    • Pa0008 604
  • Moscow, Russian Federation
    • Pa0008 605
  • Moscow, Russian Federation
    • Pa0008 607
  • Saint Petersburg, Russian Federation
    • Pa0008 606
  • Saint Petersburg, Russian Federation
    • Pa0008 608
• United States
  • California
    • San Diego, California, United States, 92037
      • Pa0008 007
  • Florida
    • Aventura, Florida, United States, 33180
      • Pa0008 005
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Pa0008 003
  • Minnesota
    • Lansing, Minnesota, United States, 48910
      • Pa0008 011
  • New York
    • Lexington, New York, United States, 40504
      • Pa0008 025
  • Oregon
    • Portland, Oregon, United States, 97239
      • Pa0008 014
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Pa0008 001
  • Rhode Island
    • Johnston, Rhode Island, United States, 02919
      • Pa0008 012
  • South Carolina
    • Charleston, South Carolina, United States, 29406-93
      • Pa0008 004
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Pa0008 010
  • Texas
    • Dallas, Texas, United States, 75231
      • Pa0008 006
    • Mesquite, Texas, United States, 75150
      • Pa0008 013
  • Washington
    • Seattle, Washington, United States, 98122
      • Pa0008 002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject has a documented diagnosis of adult-onset PsA classified by Classification Criteria for Psoriatic Arthritis (CASPAR) criteria with symptoms for at least 6 months prior to Screening, with active psoriatic arthritis (PsA) at Baseline/Day 1, and must have at Baseline tender joint count (TJC) >=3 out of 78 and swollen joint count (SJC) >=3 out of 76
• Subject must be rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies negative
• Subject must have active psoriatic lesion(s) and/or a documented history of psoriasis
• Subjects who are regularly taking nonsteroidal anti-inflammatory drug (NSAIDs)/COX-2 inhibitors as part of their PsA therapy are required to be on a stable dose/dose regimen for at least 14 days before Baseline
• Subjects taking corticosteroids must be on an average daily dose of <=10mg/day prednisone or equivalent for at least 14 days before Baseline and should remain on a stable dose through the Week 16 visit
• Subjects taking methotrexate (MTX) (<=25mg /week) are allowed to continue their medication if started at least 12 weeks prior to Baseline, with a stable dose for at least 8 weeks before randomization
• Subjects taking leflunomide (LEF; <=20mg/day or an average of 20mg/day if not dosed daily) are allowed to continue their medication if started at least 3 months prior to Baseline, with a stable dose for at least 8 weeks before randomization. Dose and dosing schedule should remain stable up to Week 16

• Subjects may be tumor necrosis factor (TNF) inhibitor naïve or may have received 1 prior TNF inhibitor. Subjects who have been on a TNF inhibitor previously must have:

  1. experienced an inadequate response to previous treatment given for at least 3 months
  2. been intolerant to administration (eg, had a side-effect/adverse event (AE) that led to discontinuation)
  3. lost access to TNF inhibitor for other reasons

Exclusion Criteria:

• Subjects with any current sign or symptom that may indicate an active infection (with the exception of the common cold) or has had an infection requiring systemic antibiotics within 2 weeks of Baseline/Day 1
• Subjects with a history of chronic or recurrent infections, or a serious or life-threatening infection within the 6 months prior to the Baseline Visit
• Subjects with concurrent acute or chronic viral hepatitis B or C or human immunodeficiency virus (HIV) infection
• Subjects with known history of or current clinically active infection with Histoplasma, Coccidioides, Paracoccidioides, Pneumocystis, Blastomyces, or Aspergillus or current active Candidiasis
• Subjects receiving any live (includes attenuated) vaccination within the 8 weeks prior to Baseline
• Subjects with known tuberculosis (TB) infection, at high risk of acquiring TB infection, with latent TB infection (LTBI), or current or history of nontuberculous mycobacteria (NTMB) infection
• Subjects with a diagnosis of inflammatory conditions other than psoriasis or psoriatic arthritis

• Subjects with concurrent malignancy or a history of malignancy during the past 5 years will be excluded, with following exceptions that may be included:

  1. <= 3 excised or ablated basal cell carcinomas of the skin
  2. One squamous cell carcinoma of the skin (stage T1 maximum) successfully excised, or ablated only (other treatments, ie, chemotherapy, do not apply), with no signs of recurrence or metastases for more than 2 years prior to Screening
  3. Actinic keratosis (-es)
  4. Squamous cell carcinoma-in-situ of the skin successfully excised, or ablated, more than 6 months prior to Screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Subjects will receive for 12 Weeks Placebo and will then be re-randomized to Bimekizumab dosage regimen 2 or Bimekizumab dosage regimen 3 for 36 Weeks.	Other: Placebo
Experimental: Bimekizumab dosage regimen 1; Subjects will receive for 12 Weeks Bimekizumab dosage regimen 1 and will then be re-randomized to Bimekizumab dosage regimen 2 or Bimekizumab dosage regimen 3 for 36 Weeks.	Drug: Bimekizumab; Bimekizumab in different dosage regimens.; Other Names: UCB4940
Experimental: Bimekizumab dosage regimen 2; Subjects will receive for 48 Weeks Bimekizumab dosage regimen 2.	Drug: Bimekizumab; Bimekizumab in different dosage regimens.; Other Names: UCB4940
Experimental: Bimekizumab dosage regimen 3; Subjects will receive for 48 Weeks Bimekizumab dosage regimen 3.	Drug: Bimekizumab; Bimekizumab in different dosage regimens.; Other Names: UCB4940
Experimental: Bimekizumab dosage regimen 4; Subjects will receive for 12 Weeks Bimekizumab dosage regimen 4 and will then be re-randomized to Bimekizumab dosage regimen 2 for 36 Weeks.	Drug: Bimekizumab; Bimekizumab in different dosage regimens.; Other Names: UCB4940

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACR50 (American College of Rheumatology 50% Improvement) Response at Week 12	The ACR50 response rate was based on 50% improvement relative to Baseline in the following measures: Tender Joint Count (TJC) based on 78 joints; Swollen Joint Count (SJC) based on 76 joints; 3 of the 5 remaining core set measures:Disease activity as assessed by Patient's Global Assessment of Disease Activity (PGADA)Disease activity as assessed by Physician's Global Assessment of Disease Activity (PhGADA)Pain as assessed by Patient's Assessment of Arthritis Pain (PtAAP)Physical function as assessed by Health Assessment Questionnaire - Disability Index (HAQ-DI)Acute phase response as assessed by high sensitivity C-reactive protein (hs CRP).	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACR20 (American College of Rheumatology 20% Improvement) Response at Week 12	The ACR20 response rate was based on 20% improvement relative to Baseline in the following measures: TJC based on 78 joints; SJC based on 76 joints; 3 of the 5 remaining core set measures:Disease activity as assessed by PGADADisease activity as assessed by PhGADAPain as assessed by PtAAPPhysical function as assessed by HAQ-DIAcute phase response as assessed by hs CRP Note: Nonresponder imputation was used to account for missing data in the primary analysis, the study participants with a missing ACR score at Week 12 or who discontinued IMP prior to the Week 12 Visit were considered nonresponders for the primary analysis.	Week 12
ACR70 (American College of Rheumatology 70% Improvement) Response at Week 12	The ACR70 response rate was based on 70% improvement relative to Baseline in the following measures: TJC based on 78 joints; SJC based on 76 joints; 3 of the 5 remaining core set measures:Disease activity as assessed by PGADADisease activity as assessed by PhGADAPain as assessed by PtAAPPhysical function as assessed by HAQ-DIAcute phase response as assessed by hs CRP Note: Nonresponder imputation was used to account for missing data in the primary analysis, the study participants with a missing ACR score at Week 12 or who discontinued IMP prior to the Week 12 Visit were considered nonresponders for the primary analysis.	Week 12
PASI90 (Psoriasis Area Severity Index) Response at Week 12 in the Subgroup of Subjects With Psoriasis Involving at Least 3 % Body Surface Area (BSA) at Baseline/Day 1	The PASI90 response assessments are based on at least 90% improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person's affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease.	Week 12
PASI75 (Psoriasis Area Severity Index) Response at Week 12 in the Subgroup of Subjects With Psoriasis Involving at Least 3 % Body Surface Area (BSA) at Baseline/Day 1	The PASI75 response assessments are based on at least 75% improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person's affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease.	Week 12
Percentage of Participants With at Least One Adverse Event (AE) During the Study	An adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP.	From Screening Period until the Safety Follow-Up Visit (up to Week 72)
Percentage of Participants With at Least One Serious Adverse Event (SAE) During the Study	A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: Results in death; Is life-threatening; Requires in patient hospitalization or prolongation of existing hospitalization; Is a congenital anomaly or birth defect; Is an infection that requires treatment parenteral antibiotics; Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above.	From Screening Period until the Safety Follow-Up Visit (up to Week 72)
Percentage of Participants Who Withdrew Due to an Adverse Event (AE) During the Study	An adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP.	From Screening Period until the Safety Follow-Up Visit (up to Week 72)
Changes From Baseline in Vital Signs During the Study (Diastolic Blood Pressure, Systolic Blood Pressure)	Diastolic and systolic blood pressure were measured in millimeters of mercury (mmHg).	Baseline, 30 min and 1 hour post dose, Week 1, Week 2, pre- and post dose for the following Weeks: 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44 and Week 48
Changes From Baseline in Vital Signs During the Study (Pulse Rate)	Pulse rate was measured in beats per minute (beats/min).	Baseline, 30 min and 1 hour post dose, Week 1, Week 2, pre- and post dose for the following Weeks: 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44 and Week 48
Changes From Baseline in Body Weight During the Study	Body weight was measured in kilograms.	Baseline, Week 12, Week 24, Week 36 and Week 48
Changes From Baseline in Electrocardiogram (ECG) Intervals During the Study (QTcB, QTcF, PR, QRS, QT, RR)	Electrocardiogram (ECG) intervals (QTcB= QT interval corrected for heart rate (Bazett's formula); QTcF= QT interval corrected for heart rate (Fridericia's formula)) were measured in milliseconds.	Baseline, Week 12 and Week 48
Changes From Baseline in Hematology Parameters During the Study (Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils)	Basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils were measured in number of white blood cells per liter (10^9/L).	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
Changes From Baseline in Hematology Parameters During the Study (Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration, Hemoglobin)	Erythrocytes mean corpuscular hemoglobin (HGB) concentration and hemoglobin were measured in grams per liter (g/L).	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
Changes From Baseline in Hematology Parameters During the Study (Erythrocytes Mean Corpuscular Hemoglobin (HGB))	Erythrocytes mean corpuscular hemoglobin (HGB) was measured in picograms (pg).	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
Changes From Baseline in Hematology Parameters During the Study (Erythrocytes Mean Corpuscular Volume)	Erythrocytes mean corpuscular volume was measured in femtolitres (fL).	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
Changes From Baseline in Hematology Parameters During the Study (Erythrocytes)	Erythrocytes was measured in number of red blood cells per liter (10^12/L).	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
Changes From Baseline in Hematology Parameters During the Study (Hematocrit)	Hematocrit was measured in volume percentage (%) of red blood cells in blood.	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
Changes From Baseline in Hematology Parameters During the Study (Platelets)	Platelets was measured in number of platelets per liter (10^9/L).	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
Changes From Baseline in Biochemistry Parameters During the Study (Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, Lactate Dehydrogenase)	Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma glutamyl transferase, lactate dehydrogenase were measured in units per liter (U/L).	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
Changes From Baseline in Biochemistry Parameters During the Study (Albumin)	Albumin was measured in grams per liter (g/L).	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
Changes From Baseline in Biochemistry Parameters During the Study (Bilirubin, Creatinine, Urate)	Bilirubin, creatinine, urate were measured in micromols per liter (μmol/L).	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
Changes From Baseline in Biochemistry Parameters During the Study (Calcium, Chloride, Cholesterol, Glucose, Magnesium, Potassium, Sodium)	Calcium, chloride, cholesterol, glucose, magnesium, potassium, sodium were measured in millimoles per liter (mmol/L).	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
Changes From Baseline in Biochemistry Parameters During the Study (Urea Nitrogen)	Urea nitrogen was measured in millimoles per liter (mmol/L).	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
Changes From Baseline in Urinalysis Parameters During the Study (Erythrocytes, Leukocytes, Renal Epithelial Casts, Squamous Epithelial Cells, Transitional Epithelial Cells)	Erythrocytes, leukocytes, renal epithelial casts, squamous epithelial cells, transitional epithelial cells were measured in cells per high power field (cells/HPF).	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
Changes From Baseline in Urinalysis Parameters During the Study (Hyaline Casts)	Hyaline casts was measured in cells per low power field (cells/LPF).	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48
Changes From Baseline in Urinalysis Parameters During the Study (pH)	Urine pH was measured on a pH scale.	Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48

Collaborators and Investigators

• Sponsor: UCB Biopharma S.P.R.L.

Publications and helpful links

General Publications

• Ritchlin CT, Kavanaugh A, Merola JF, Schett G, Scher JU, Warren RB, Gottlieb AB, Assudani D, Bedford-Rice K, Coarse J, Ink B, McInnes IB. Bimekizumab in patients with active psoriatic arthritis: results from a 48-week, randomised, double-blind, placebo-controlled, dose-ranging phase 2b trial. Lancet. 2020 Feb 8;395(10222):427-440. doi: 10.1016/S0140-6736(19)33161-7.
• Mease PJ, Asahina A, Gladman DD, Tanaka Y, Tillett W, Ink B, Assudani D, de la Loge C, Coarse J, Eells J, Gossec L. Effect of bimekizumab on symptoms and impact of disease in patients with psoriatic arthritis over 3 years: results from BE ACTIVE. Rheumatology (Oxford). 2023 Feb 1;62(2):617-628. doi: 10.1093/rheumatology/keac353.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): July 1, 2018

Study Registration Dates

• First Submitted: November 10, 2016
• First Submitted That Met QC Criteria: November 16, 2016
• First Posted (Estimate): November 21, 2016

Study Record Updates

• Last Update Posted (Actual): March 20, 2023
• Last Update Submitted That Met QC Criteria: March 17, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Psoriatic Arthritis; PsA; Bimekizumab
• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic
• Other Study ID Numbers: PA0008; 2016-001103-23 (EudraCT Number)